DCT

1:24-cv-00138

Bayer Pharma AG v. Lupin Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00138, D. Del., 02/02/2024
  • Venue Allegations: Venue is alleged to be proper as Lupin Pharmaceuticals, Inc. is a Delaware corporation, and Lupin Limited is subject to personal jurisdiction in the district as an alien defendant.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the 2.5 mg XARELTO® product constitutes an act of infringement of a patent covering a method of treatment.
  • Technical Context: The technology involves a specific combination drug therapy—the anticoagulant rivaroxaban and aspirin—used to reduce the risk of major cardiovascular events in patients with coronary or peripheral artery disease.
  • Key Procedural History: This action follows a prior lawsuit between the same parties over the same patent, Bayer Pharma AG et al. v. Lupin Limited et al., C.A. No. 21-314-RGA (D. Del.), which was initiated after Lupin’s first notice letter. In that prior action, Lupin stipulated to infringement of the patent-in-suit. The current complaint was filed after Plaintiffs received a second notice letter from Lupin regarding its ANDA.

Case Timeline

Date Event
2018-02-02 U.S. Patent No. 10,828,310 Priority Date
2020-11-10 U.S. Patent No. 10,828,310 Issue Date
2021-01-15 Lupin sends First Notice Letter regarding ANDA No. 208555
2021-03-01 Plaintiffs file prior infringement suit against Lupin
2023-12-21 Lupin sends Second Notice Letter to Plaintiffs
2024-02-02 Complaint Filing Date

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 10,828,310 - "REDUCING THE RISK OF CARDIOVASCULAR EVENTS," issued November 10, 2020

The Invention Explained

  • Problem Addressed: The patent's background section describes the high risk of major adverse cardiovascular events (e.g., heart attack, stroke) faced by patients with coronary artery disease (CAD) and peripheral artery disease (PAD). It notes that prior to the invention, anticoagulant therapies had not demonstrated superiority over standard antiplatelet therapy (aspirin) without also causing unacceptably high rates of major bleeding (’310 Patent, col. 2:2-22).
  • The Patented Solution: The invention is a method of treatment based on the discovery that a specific combination therapy—a low dose of the factor Xa inhibitor rivaroxaban co-administered with a low dose of aspirin—is effective at reducing the risk of major cardiovascular events in this patient population (’310 Patent, Abstract; col. 3:50-55). The patent specification directly links this discovery to the results of the large-scale phase III COMPASS clinical trial (’310 Patent, col. 3:26-34).
  • Technical Importance: The claimed method provided a novel therapeutic regimen that demonstrated a statistically significant improvement in efficacy over the then-current standard of care for a large patient population, addressing a long-standing need for more effective treatments (’310 Patent, col. 2:27-30).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶41).
  • Claim 1 requires:
    • A method of reducing the risk of myocardial infarction, stroke or cardiovascular death in a human patient with coronary artery disease and/or peripheral artery disease,
    • comprising administering to the human patient rivaroxaban and aspirin in amounts that are clinically proven effective in reducing said risk,
    • wherein rivaroxaban is administered in an amount of 2.5 mg twice daily,
    • and aspirin is administered in an amount of 75-100 mg daily.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Lupin's generic 2.5 mg rivaroxaban tablet, for which it seeks FDA approval via ANDA No. 208555 ("Lupin's ANDA Product") (Compl. ¶¶ 9, 33).

Functionality and Market Context

  • The infringement allegation is based on the future, intended use of Lupin's ANDA Product as directed by its proposed labeling (Compl. ¶38). The complaint alleges that this proposed label will instruct healthcare providers and patients to use the 2.5 mg rivaroxaban tablets in a manner that practices the patented method. Specifically, the label allegedly directs administration of the product twice daily in combination with 75-100 mg of aspirin for reducing the risk of major cardiovascular events in patients with CAD or PAD (Compl. ¶38). The filing of the ANDA itself is the statutory act of infringement under 35 U.S.C. § 271(e)(2), aimed at securing approval to market a generic version of Plaintiffs' XARELTO® product before the ’310 patent expires (Compl. ¶¶ 1, 45). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'310 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of reducing the risk of myocardial infarction, stroke or cardiovascular death in a human patient with coronary artery disease and/or peripheral artery disease, The proposed labeling for Lupin's ANDA Product allegedly directs a method for "reducing the risk of major cardiovascular events (cardiovascular (CV) death, myocardial infarction (MI), and stroke) in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD)." ¶38 col. 3:56-62
comprising administering to the human patient rivaroxaban and aspirin in amounts that are clinically proven effective in reducing the risk of myocardial infarction, stroke or cardiovascular death in a human patient with...disease, Lupin's ANDA Product contains rivaroxaban, and its proposed labeling allegedly directs its administration in combination with aspirin in amounts that are clinically proven effective for the claimed purpose. ¶35, ¶38 col. 4:5-10
wherein rivaroxaban is administered in an amount of 2.5 mg twice daily Lupin's ANDA Product is a 2.5 mg rivaroxaban tablet, and the proposed labeling allegedly directs that it "be administered twice daily." ¶33, ¶38 col. 4:9-10
and aspirin is administered in an amount of 75-100 mg daily. The proposed labeling for Lupin's ANDA product allegedly directs that aspirin "is administered in an amount of 75-100 mg daily." ¶38 col. 4:10-11
  • Identified Points of Contention:
    • Technical Questions: The complaint alleges that Lupin's proposed label directs administration that maps directly onto each element of claim 1. Given that Lupin previously stipulated to infringement of this patent, a primary question for the court is whether any aspect of Lupin's amended ANDA or proposed labeling has changed in a way that would materially alter the infringement analysis from the prior litigation. The complaint does not detail any such changes.
    • Scope Questions: In any ANDA case based on induced infringement, a central question is whether the proposed label's instructions will inevitably lead physicians to prescribe, and patients to use, the drug in an infringing manner. The court will examine whether the proposed label for Lupin's product actively encourages and instructs the specific combination therapy recited in the claim for the specified patient population.

V. Key Claim Terms for Construction

  • The Term: "clinically proven effective"
  • Context and Importance: This term appears in the second element of claim 1 and links the administration of the drugs to a standard of evidentiary proof. Practitioners may focus on this term because its construction could influence both infringement and validity. A defendant could argue the term is indefinite under 35 U.S.C. § 112, or attempt to define it narrowly in a way that distinguishes it from prior art or from the effects described in the accused product's label.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Plaintiffs may argue the term should be understood in the context of the patent as a whole, which presents the results of the COMPASS trial as the clinical proof of efficacy. The specification states that the invention "concerns the discovery that combination therapy...shows efficacy" and proceeds to describe the specific dosages found to be effective, suggesting the patent itself embodies the clinical proof (’310 Patent, col. 3:50-55).
    • Evidence for a Narrower Interpretation: A defendant may argue that the term is tied specifically and exclusively to the patient population, protocols, and statistical outcomes of the COMPASS trial as detailed in the patent specification (’310 Patent, col. 3:26-40, col. 13:35-14:4). Such a narrow construction could be used to argue that any deviation in a real-world patient or a slight difference in a label's indication falls outside the claim's scope.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement claim is based on allegations that Lupin’s proposed product labeling will actively instruct and encourage physicians and patients to perform the patented method (Compl. ¶¶ 38, 43). The contributory infringement claim alleges that Lupin's product, together with its label, is especially made for an infringing use and is not suitable for a substantial noninfringing use (Compl. ¶44).
  • Willful Infringement: Willfulness is alleged based on Lupin's knowledge of the ’310 patent, which the complaint states existed since at least the date of its first Paragraph IV notice letter on January 15, 2021 (Compl. ¶¶ 33, 42). The prior lawsuit on the same patent is presented as further evidence of knowledge and intent (Compl. ¶36).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A central issue will be the preclusive or persuasive effect of the prior litigation. Given that Lupin previously stipulated to infringement of the '310 patent, the court will likely need to determine why this second lawsuit is necessary and to what extent Lupin may be constrained from re-litigating infringement, focusing the case primarily on its patent validity challenges.
  • The case may turn on a question of inducement and label interpretation. Assuming the patent is valid, the court will need to decide if the instructions in Lupin's proposed drug label are sufficiently specific to actively encourage and direct healthcare providers to prescribe, and patients to use, the generic product in a manner that directly practices every step of the claimed method.
  • A key battleground, if infringement is not the primary focus, will be patent validity. The core question will be whether the claimed combination therapy—a 2.5 mg twice-daily dose of rivaroxaban with a 75-100 mg daily dose of aspirin—was obvious or anticipated by the prior art at the time of the invention, despite the clinical trial results presented in the patent.